Reproduction in cattle can be inefficient, owing to a variety of factors including herd size and that cows in estrus are not always observed.
Previous artificial insemination (AI) protocols have been attempted, using multiple drug substances. Examples of previously attempted AI protocols are as follows:
Number ofinterventions*Name of Protocolincluding AINumber of Drugs Used**7 day CO-Synch327 day CO-Synch + CIDR337 day OV-Synch + CIDR435 day OV-Synch + CIDR43MGA-Select437-11 Synch53*Refers to the number of separate occasions on which the cows must be handledIn some protocols, more than one dose of a drug is administered.
However, AI programs remain inefficient. Such inefficiencies result in lower insemination frequencies, which reduces economic efficiencies. This is a significant problem in cattle reproduction.
Among the strategies used to control ovarian function in cattle, treatment with estrogen in combination with progesterone has been very effective for synchronizing follicle wave emergence and ovulation [1, 2]. Steroid-induced wave synchronization is brought about by regression of the dominant follicle followed by resurgence in circulating FSH and subsequent emergence of a new follicular wave at a consistent interval post-treatment. Steroid-induced regression of the dominant follicle is a result of a systemic alteration in feedback of estradiol and progesterone on pituitary release of LH and FSH [3]. Estradiol suppresses FSH release [4], and decreases LH pulse amplitude in sheep [5] and cattle [6]. Progesterone decreases LH pulse frequency and suppresses growth of the dominant follicle in a dose-dependent manner in cattle [7-12]. After metabolic clearance of exogenous estradiol, endogenous FSH surges therefore resulting in the emergence of a new wave of follicular development approximately 4 days after estradiol/progesterone treatment regardless of the stage of development of the dominant follicle at the time of treatment [1, 2, 13].
The use of natural or synthetic estrogens in food producing animals, however, has been the subject of considerable controversy (reviewed in [18]). Increasing concern regarding the toxicity of hormonal preparations used as growth promotants in cattle and the potential carcinogenic effects of steroid hormone residues in meat or milk [19-21] has led to a prohibition of the use of estradiol and other steroid hormones as growth promotants in animals designated for human consumption in all the member states of the European Union as of Jan. 1, 1989 [22]. Furthermore, the use of estradiol-1713 and its ester derivatives for purposes of reproductive management was prohibited in the European Union on Oct. 14, 2006 [23]. These actions in Europe led to the subsequence prohibition of the use of estradiol esters in lactating dairy animals in New Zealand and Australia in 2007 [24]. Although the use of estradiol and zeranol (an estrogen-like compound) as growth promotants is still permitted in the United States [25] and Canada [26], they cannot be used for the purpose of estrus synchronization except by prescription and custom-compounding. However, veterinary compounding of pharmaceuticals for food-producing animals has recently come under scrutiny in the US and is discouraged [27, 28]. This situation negatively impacts the implementation of reproductive technologies in cattle production systems, limiting potential reproductive efficiency and genetic improvement provided by the use of artificial insemination and embryo transfer [24].
In this context, the development of alternative methods for controlling ovarian function in cattle is needed.
This background information is provided for the purpose of making known information believed by the applicant to be of possible relevance to the present invention. No admission is necessarily intended, nor should it be construed, that any of the preceding information constitutes prior art against the present invention.